Introduction: Majority of HbE/β-thalassaemia patients resembles the phenotype of non-transfusion dependent thalas- saemia (NTDT). Current management strategies are highly diverse, and the objective of this study is to examine the effects of different treatments on multiple parameters in NTDT HbE/β-thalassaemia to further streamline the manage- ment of this disorder. Methods: In this cross-sectional study, we analysed the correlation between different treatment strategies with variable parameters including haematological parameter and globin gene expression. Statistical analyses were carried out using non-parametric tests such as Kruskal-Wallis and Mann-Whitney tests. Results: A total of 29 HbE/β-thalassaemia patients were included in the study. Data showed statistically significant differences were observed in the MCV, MCHC levels, reticulocyte count and log α/β fold change between the groups. Further analysis showed higher log α/β fold change in the transfusion only group compared to the non-treated group. Red blood cell count was found to be lower in transfused and splenectomised group compared to transfusion only. Sig- nificantly higher MCV level and reticulocyte count was seen in transfusion and splenectomised group compared to both non-treated and transfusion only groups and higher MCH level in the transfusion and splenectomised group compared to transfusion only group. Conclusion: In general, regardless of single or double combined therapies, HbE/β-thalassaemia showed variable changes in laboratory parameters to the therapies received particularly sple- nectomy.